The advent of colonoscopy brought with it the need for a simplified, routine bowel cleansing protocol or product to achieve a clean colonic mucosa required by the colonoscopist to detect even small lesions in the bowel, e.g. small polyps. Similar requirements exist for colonic surgery.
In the early days of colonoscopy, during the late 1970's, numerous protocols for bowel cleansing were designed by individual bowel surgeons and gastroenterologists to satisfy the requirements of their particular practices. Such protocols included the use of fasting in combination with various purgatives such as Epsom salts or osmotic agents plus enemas. Though, when complex protocols were followed strictly they often achieved their effect and resulted in a clean bowel. However, the protocols were invariably complex and required on average 3 days of cleansing which made them unpleasant and unacceptable. Furthermore, they were often dangerous because they caused marked fluid and electrolyte shifts in body compartments and on rare occasions predisposed to arrythmias, hypertension and in fact demise of the patient.
To overcome the problem of fluid shifts, Fordtrau developed an orthostatic lavage which combined with a large muscular, non-absorbable polyethylene glycol (PEG) compounded with a balanced electrolyte solution resembling concentrations found in the human serum. Such a lavage achieved very adequate levels of bowel cleansing, with minimal fluid and electrolyte shifts but at the expense of patient compliance and acceptability. PEG solutions produce volumogenic diarrhoea, by requiring ingestion of large volumes of the electrolyte solution. Finally 4 to 5 liters of the solution are required to obtain adequate cleansing for colonoscopy or bowel surgery. With such large volumes being drunk by the patient and with the taste of the electrolyte and PEG being particularly unpleasant, patients frequently experienced nausea, vomiting and bloating. Those requiring a colonoscopy on repeated occasions would clearly identify the PEG lavage as the most unpleasant aspect of colonoscopy. On occasions the level of discomfort caused by the cleansing lavage proved to be counter productive to reaching the desired aim of colonic cleansing, as patients would terminate ingesting the PEG solution, either due to the bad taste or nausea/vomiting.
It was for the above reasons that an effort was made to develop a favourable flavouring for the PEG lavage solution, and to reduce the need for large volume ingestion from 4 to 3 liters This was achieved by adding ascorbic acid, which acted as both a flavouring agent and a diarrheogenic compound reducing the volume required for ingestion from 4 to 3 liters. This improvement resulted in the Australian Patent No. 623,627 and equivalent US and European patents. Nevertheless, the still large volume of solution (3 liters) required to cleanse the bowel remained an obstacle to adequate cleansing in some patients.
As a result, there developed a shift back to osmotic diarrheogenic agents which required the patient to ingest a small volume of foul tasting electrolyte buffered solution (eg. phosphate based FLEET laxative) which would extract by osmotic tension a large volume of fluid from the patient's body and cause diarrhoea. There was therefore a clear advantage with this approach, since the patients did not need to keep on drinking a large volume of bad-tasting solution. However, osmotically active agents were notorious for causing electrolyte and fluid shifts, resulting in marked weight loss, hyperphosphataemnia and death in children, arrythmias and cardiac deaths in the more frail elderly patients. The side effects of nausea/vomiting continued to be a problem. To overcome the massive fluid shifts without the patient undergoing cleansing, the phosphate-based products were marketed to be combined with the ingestion of large volumes of pleasant-tasting glucose-free liquids such as water or mineral water. This exogenous input of a volume of water helped to effect fluid shifts. A portion of the fluid for the diarrheogenic effect originated in patients body fluids, while the remainder came from ungested water. Several trials covering palatability and effectiveness of the PEG versus Phosphate solutions, reached the conclusion that both can achieve comparable bowel cleansing and both continue to suffer from unpleasant taste and excessive volume.
Yet another problem to overcome has been the development of hyperphosphataemia and dehydration with potential of arrythmias and resulting syncope and reports of deaths--especially in children. With the small volume of the currently available phosphate-based evacuants, patients are able to drink simply the evacuant and not follow on with any further water. It would be therefore prudent to build in a safety system whereby numerous capsules will have to be swallowed with a fair volume of water to prevent the concentrating effect of the diarrhoea.
It would therefore be of advantage to develop a product which could be free of "foul tasting fluid" and yet achieve bowel cleansing while drinking acceptable amounts of liquids such as water, dietary soft drinks or mineral water.
A further problem which frequently presents itself during diagnostic colonoscopy is the foam-like bubbles which obstruct the viewing clarity, especially in the proximal colon. This foaming is a phenomenon caused by the rapid passage into the colon of bile secreted into the lumen of the bowel by the liver. In a proportion of patients, the caecum and especially the ascending colon are almost totally covered by a film of bile-containing foam, precluding a clear view of the mucosa. Such obstruction of view has on occasions led to a mis-diagnosis by the colonoscopist of colonic polyps and small cancers. Therefore there is a need to prevent foaming within the colon during the cleansing process. This has been attempted by injecting anti-foaming agents into the colon during colonoscopy. This method can achieve local de-foaming, but it is time consuming and rarely adequate. There is a need therefore to include an anti-foaming agent into the bowel-preparation formulation, to achieve uniform anti-foaming throughout the 1 meter length of the colon.
The objective of the present invention is to overcome the above-mentioned problems, of bad taste and foaming without sacrificing the excellent bowel-cleansing characteristics of the phosphate-based lavage solution. An added effect of adding an anti-foaming agent is the increase in lubrication of the colonic surface, thereby facilitating speed of colonoscopy to the caecum.